[Editors] MIT probe may help untangle cells’ signaling pathways

[Elizabeth Thomson]

For Immediate Release
FRIDAY, JUN. 27, 2008

Contact: Elizabeth A. Thomson, MIT News Office
T. 617-258-5402   E.: thomson at mit.edu

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MIT probe may help untangle cells’ signaling pathways
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CAMBRIDGE, Mass.--MIT researchers have designed a new type of probe  
that can image thousands of interactions between proteins inside a  
living cell, giving them a tool to untangle the web of signaling  
pathways that control most of a cell’s activities.

“We can use this to identify new protein partners or to characterize  
existing interactions. We can identify what signaling pathway the  
proteins are involved in and during which phase of the cell cycle the  
interaction occurs,” said Alice Ting, the Pfizer-Laubach Career  
Development Assistant Professor of Chemistry and senior author of a  
paper describing the probe published online June 27 by the Journal of  
the American Chemical Society.

The new technique allows researchers to tag proteins with probes that  
link together like puzzle pieces if the proteins interact inside a  
cell. The probes are derived from an enzyme and its peptide  
substrate. If the probe-linked proteins interact, the enzyme and  
substrate also interact, which can be easily detected.

To create the probes, the researchers used the enzyme biotin ligase  
and its target, a 12-amino-acid peptide.

Their work is conceptually related to an approach that uses GFPs  
(green fluorescent proteins), which glow when activated, as probes.  
Half of each GFP molecule is attached to the proteins of interest,  
and when the proteins interact, the GFP halves fuse and glow.  
However, this technique results in many false positives, because the  
GFP halves seek each other out and bind even when the proteins they  
are attached to are not interacting, said Ting.

The new probes could be used to study nearly any protein-protein  
interaction, Ting said. The researchers tested their probes on two  
signaling proteins involved in suppression of the immune system, and  
on two proteins that play a role in cell division. They are currently  
using the probe to image the interaction of proteins involved in  
synapse growth in live neurons.

Lead author of the paper is Marta Fernandez-Suarez, a graduate  
student in chemistry. Biology graduate student T. Scott Chen is also  
an author of the paper.

The research was funded by the National Institutes of Health and the  
McKnight, Dreyfus and Sloan Foundations.

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Written by Anne Trafton, MIT News Office